Comparison of Comorbidities between Adults and Children with Glycogen Storage Disease Type Ia (GSDIA)

Objectives: Glycogen Storage Disease Type Ia (GSDIa) is a rare inherited disorder resulting in acute hypoglycemia due to impaired release of glucose from glycogen. Despite dietary management practices to prevent hypoglycemia in patients with GSDIa, complications still occur in children and throughout adulthood. This retrospective cohort study compared the prevalence of complications in adults and children with GSDIa. Method(s): Using ICD-10 diagnosis codes, the IQVIA Pharmetrics Plus database was searched for patients with >=2 GSDI claims (E74.01) from January 2016 through February 2020, with >=12 months continuous enrollment beginning prior to March 2019 (for one year of follow-up before COVID-19), and no inflammatory bowel disease diagnoses (indicative of GSDIb). Complication prevalence in adults and children with GSDIa was summarized descriptively. Result(s): In total, 557 patients with GSDIa were identified (adults, 67%;male, 63%), including 372 adults (median age, 41 years) and 185 children (median age, 7 years). Complications occurring only in adults were atherosclerotic heart disease (8.6%), pulmonary hypertension (3.0%), primary liver cancer (1.9%), dialysis (0.8%), and focal segmental glomerulosclerosis (0.3%). Other complications with the greatest prevalence in adults/children included gout (11.8%/0.5%), insomnia (10.0%/1.1%), osteoarthritis (22.0%/2.7%), severe chronic kidney disease (4.3%/0.5%), malignant neoplasm (10.8%/1.6%), hypertension (49.7%/8.7%), acute kidney failure (15.3%/2.7%), pancreatitis (3.0%/0.5%), gallstones (7.8%/1.6%), benign neoplasm (37.4%/8.1%), hepatocellular adenoma (7.0%/1.6%), neoplasm (41.1%/9.7%), and hyperlipidemia (45.2%/10.8%). Complications with the greatest prevalence in children/adults included poor growth (22.2%/1.9%), gastrostomy (29.7%/3.2%), kidney hypertrophy (2.7%/0.8%), seizure (1.6%/0.5%), hypoglycemia (27.0%/11.3%), hepatomegaly (28.7%/15.9%), kidney transplant (1.6%/1.1%), diarrhea (26.5%/18.6%), nausea and/or vomiting (43.8%/35.8%), acidosis (20.0%/17.2%), and anemia due to enzyme disorders (43.8%/40.6%). Conclusion(s): GSDIa is associated with numerous, potentially serious complications. Compared with children, adults with GSDIa had a greater prevalence of chronic complications, potentially indicating the progressive nature of disease. Children with GSDIa had more acute complications related to suboptimal metabolic control.Copyright © 2023

The metabolic effects of APOL1 in humans.

Harboring apolipoprotein L1 (APOL1) variants coded by the G1 or G2 alleles of the APOL1 gene increases the risk for collapsing glomerulopathy, focal segmental glomerulosclerosis, albuminuria, chronic kidney disease, and accelerated kidney function decline towards end-stage kidney disease. However, most subjects carrying APOL1 variants do not develop the kidney phenotype unless a second clinical condition adds to the genotype, indicating that modifying factors modulate the genotype-phenotype correlation. Subjects with an APOL1 high-risk genotype are more likely to develop essential hypertension or obesity, suggesting that carriers of APOL1 risk variants experience more pronounced insulin resistance compared to noncarriers. Likewise, arterionephrosclerosis (the pathological correlate of hypertension-associated nephropathy) and glomerulomegaly take place among carriers of APOL1 risk variants, and these pathological changes are also present in conditions associated with insulin resistance, such as essential hypertension, aging, and diabetes. Insulin resistance may contribute to the clinical features associated with the APOL1 high-risk genotype. Unlike carriers of wild-type APOL1, bearers of APOL1 variants show impaired formation of lipid droplets, which may contribute to inducing insulin resistance. Nascent lipid droplets normally detach from the endoplasmic reticulum into the cytoplasm, although the proteins that enable this process remain to be fully defined. Wild-type APOL1 is located in the lipid droplet, whereas mutated APOL1 remains sited at the endoplasmic reticulum, suggesting that normal APOL1 may participate in lipid droplet biogenesis. The defective formation of lipid droplets is associated with insulin resistance, which in turn may modulate the clinical phenotype present in carriers of APOL1 risk variants.

Nephrotic Syndrome in Adult Patients With COVID-19 Infection or Post COVID-19 Vaccine: A Systematic Review.

Nephrotic syndrome is a condition characterized by damage to podocytes that results in significant proteinuria, edema, hyperlipidemia, and hypercoagulability. Infections and malignancies are frequently associated with nephrotic syndrome. The COVID-19 virus has been associated with several atypical presentations of upper respiratory infections and acute kidney injury. Considering that COVID-19 causes systemic inflammatory changes, it seems plausible that it may also lead to nephrotic syndrome. This study aimed to investigate if an association between COVID-19 and the different types of nephrotic syndromes exists. Data were extracted into a spreadsheet. Statistical analysis was performed using Statistical Package for Social Sciences (SPSS, IBM Corp., Armonk, NY, USA). We performed a systematic search of PubMed/Medline and Embase databases using both medical subject headings (MeSH) and regular keywords associated with COVID-19 and nephrotic syndrome, including different types of nephrotic syndromes. The search was performed on 17th December 2021. We included case reports and case series about adult patients who developed findings suggestive of nephrotic syndrome shortly after infection or vaccination. We excluded cases involving children, pregnant women, articles written in languages other than English, and those that were not retrievable. The relevance and quality of identified articles were assessed. We included 32 articles in the study, primarily case reports and case series. In our study, COVID-19 and the COVID-19 vaccine have been associated with the development of nephrotic syndrome, primarily a collapsing form of focal segmental glomerulosclerosis, although other forms have been observed as well. There was little consistency in patient histories, clinical presentations, clinical courses, or treatment regimens, although it appeared that most cases eventually resolved. More cases need to be reported and analyzed before more definitive conclusions can be reached. In conclusion, nephrotic syndrome is a possible complication of both COVID-19 infection and the COVD-19 vaccine and should be considered in patients exhibiting sudden onset edemas or deterioration in kidney function. While the majority of cases respond to standard treatment, clearer guidelines will need to be developed once more data is available.

Collapsing glomerulonephritis in a COVID-19 patient. Case report

Acute renal injury due to collapsing glomerulonephritis is associated with high morbidity and mortality, requiring chronic dialysis, COVID-19 is one of its causes. A 17-year-old male patient presented with a four-month history of edema, foamy urine and reduction in the urine flow;anasarca was observed at physical examination. Laboratory values showed creatinine 4,2 mg/dl;albumin 1,9 gr/dl;cholesterol and triglycerides were high;proteinuria 6,7 gr/24h: leucocyturia and hematuria with negative urine culture. Serologies for HIV, syphilis and hepatitis were negative. Studies for systemic lupus were negative. An antigenic test for SARS-CoV-2 was positive as well as an IgG. Renal Biopsy showed Focal and Segmental Glomerulosclerosis, Collapsing variant. He received corticosteroids and cyclosporine. Creatinine improved;proteinuria remained >3 gr/24 hours.Copyright © Universidad Peruana Cayetano Heredia, Facultad de Medicina Alberto Hurtado. All Rights Reserved.

A Case of COVID-19-Associated Focal Segmental Glomerulosclerosis.

This case report details a 43-year-old female diagnosed with the collapsing variant of focal segmental glomerulosclerosis (FSGS) post-infection with coronavirus disease 2019 (COVID-19). The patient contracted COVID-19 after returning from a trip to Florida and initially presented to the emergency department with gastrointestinal symptoms. Thereafter, the patient was diagnosed with COVID-19 and was admitted for acute kidney injury and worsening COVID-19 infection. FSGS is a glomerulopathy that consists of glomerular scarring that leads to nephrotic syndrome, secondary to podocyte effacement. FSGS has many causes, as well as distinct variants, but is noted to have an association with some viruses, most notably HIV and cytomegalovirus (CMV). Although the association between FSGS and HIV or CMV is well established, the evidence is minimal in regard to other viruses. This case report serves to highlight the potential association of COVID-19 with FSGS.

Sequential rituximab therapy sustains remission of nephrotic syndrome but carries high risk of adverse effects.

BACKGROUND: Sequential rituximab (RTX) administration has emerged as an important strategy to sustain remission of disease in patients with difficult-to-treat nephrotic syndrome. METHODS: We report the efficacy and safety of sequential therapy with two or more courses of intravenous RTX in 250 patients with difficult-to-treat steroid dependence (n = 127) and calcineurin inhibitor (CNI)-dependent or CNI-refractory steroid resistance (n = 123) managed at one center during 2015-2021. Subsets of patients were cross-sectionally tested for hypogammaglobulinemia, seroprotection against and hyporesponsiveness to vaccines for hepatitis B and tetanus, BK/JC viruria and human antichimeric antibodies (HACAs). RESULTS: Sequential RTX therapy, initiated at a median of 10 years [interquartile range (IQR) 7.3-14.4], was administered for 1.8 courses/person-year [95% confidence interval (CI) 1.7-2.0] over 2.0 years (95% CI 1.2-3.0). Therapy was associated with postponement of relapses by a median of 3 years in patients with steroid-sensitive disease and 2 years in those with steroid resistance. Relapses were reduced by a mean of 2.0 relapses/person-year (95% CI 1.8-2.2), enabling a reduction in prednisolone dose to 0.04 mg/kg/day (95% CI 0.01-0.11) and withdrawal of additional immunosuppression in 154 (62%) patients. RTX-associated adverse events, occurring at 0.20 events/person-year (95% CI 0.17-0.23), were chiefly comprised of infusion reactions (n = 108) and infections (n = 46); serious adverse events were observed in 10.8% patients, at 0.03 events/person-year (95% CI 0.02-0.05). Hypogammaglobulinemia was observed in 35% of 177 patients and was moderate to severe in 8.5% of cases. Rates of seroprotection at baseline and response following vaccination were lower for hepatitis B [1.9% and 29.4% (n = 52)] than tetanus [65.5% and 34.5% (n = 58)]. BK/JC viruria, without viremia, was observed in 7.3% of 109 cases. A total of 19 of 107 patients (17.8%) had HACAs, which were associated with B cell nondepletion and serum sickness. Age at therapy of <9-10 years was associated with a risk of early relapse, treatment failure and hypogammaglobulinemia following RTX therapy. CONCLUSIONS: Sequential therapy with RTX effectively reduces relapses in patients with difficult-to-treat steroid- and/or CNI-dependent or CNI-refractory nephrotic syndrome. Therapy is associated with high rates of hypogammaglobulinemia and infusion reactions.

Sarcoidosis-Associated Immune Thrombocytopenic Purpura and Focal Segmental Glomerulosclerosis

Purpose of study A 32-years old male with known multi-system sarcoidosis in remission for 5 years off treatment presented to the emergency room with complaints of generalized weakness, hematemesis, epistaxis, and bruises. Physical examination was notable for petechiae, ecchymosis along with papules and plaques suggestive of active sarcoid skin lesions on his extremities. Laboratory workup was significant for thrombocytopenia 3000/uL, acute kidney injury with sub-nephrotic proteinuria. Peripheral blood smear did not show evidence of hemolysis and direct Coombs test was negative. Infectious workup including COVID-19, HIV, and hepatitis serologies were negative. Computed Tomography (CT) of chest, abdomen, and pelvis showed mild splenomegaly and an increased number of sub-centimeter hilar and mediastinal lymph nodes. The patient was treated with dexamethasone 40 mg daily for 4 days and intravenousimmunoglobulins (IVIG-2 gm/kg) for possible Immune Thrombocytopenic Purpura (ITP) with improvement in platelet count to 42000/uL by day 3. His workup for AKI and sub-nephrotic proteinuria was negative apart from a positive ANA (1: 160) with low complements. The anti-phospholipid antibody panel was negative. The ACE level was markedly elevated (>80U/L). The patient could not get a renal biopsy due to severe thrombocytopenia. He was discharged but was re-admitted in 15 days for severe thrombocytopenia of 1000/uL, epistaxis, and bruising. We continued high dose steroids along with IVIG 1 gm/kg for refractory ITP with minimal response and started anti-CD20 agent (Rituximab) 375 mg/m2 weekly with thrombopoietin-receptor agonist (Eltrombopag). His platelets count improved in response to treatment and subsequent renal biopsy showed focal and segmental glomerulosclerosis along with mild interstitial fibrosis, tubular atrophy thought to be from long standing sarcoidosis. There was also evidence of focal arteriosclerosis with no evidence of granulomas, immune complex, complement, or IgG4 deposition. Given skin lesions, thrombocytopenia, extensive lymphadenopathy, and renal involvement with markedly elevated ACE levels the overall picture was consistent with active multi-system sarcoidosis. His platelet count increased to 177,000/uL at the time of discharge. Currently, the patient is on slow steroid taper along with Eltrombopag 25 mg every other day without any recurrence of his symptoms so far. Methods used We described one case of sarcoidosis with hematologic and renal involvement. Summary of results Our patient developed hematologic and renal complications approximately 6 years after being diagnosed with sarcoidosis. Initially, he did not demonstrate sufficient clinical response to IVIG and high dose steroids. However, after a course of anti-CD20 agent (Rituximab) and with the addition of thrombopoietin-receptor agonist (Eltrombopag) he showed improvement of platelet count and stabilization of the renal function. Currently, the patient is receiving maintenance therapy with Prednisone 7.5 mg daily along with Eltrombopag 25 mg twice weekly with no recurrence of ITP and stable renal function. A further decision on whether the patient needs another cycle of Rituximab will be determined by the patient's clinical course. Conclusions Highly variable manifestations of Sarcoidosis can pose a significant diagnostic and therapeutic challenge as can be seen from our case. ITP is a rare hematological manifestation of sarcoidosis and addition of anti-CD20 agents should be considered in refractory cases.

WCN23-1206 Glomerulopathies Biobank in Uruguay. Description of the first 110 patients enrolled

Introduction: The incidence of glomerular diseases varies across different countries and criteria for kidney biopsy has changed over time. In Uruguay, glomerular diseases (GD) are a frequent cause of end stage kidney disease (ESKD) and renal replacement therapy with an annual incidence of 25.0 patients per million population according to data from the Uruguayan Dialysis Registry (UDR, year 2020). Since 1970, the Uruguayan Registry of Glomerulopathies has been recording the incidence, epidemiology and evolution of patients with GP in our country. In 2018, the Glomerulopathies Biobank (GB) began to operate including all patients with a native kidney biopsy performed at the Nephrology Department of the teaching hospital Hospital de Clinicas in Montevideo, Uruguay. The purpose of the BG is to record the phenotype (clinical and paraclinical) of patients with GD diagnosed by renal biopsy and at the same time store blood, urine, renal tissue and DNA samples. The aim of this report is to communicate the first 110 patients enrolled in the BG, which started in February 2018. Method(s): The BG protocol includes the collection of patronymic data, personal history, and clinical and paraclinical features of renal pathology. Plasma, urine and cell samples are stored for subsequent DNA extraction at the time of the kidney biopsy. In our country, all renal biopsies are performed by nephrologists. The Glomerular Biobank project is funded by the Nephrology Research Fund (School of Medicine, University of the Repubic) and was approved by the Ethics Committee of the Hospital de Clinicas and the Regulatory Verification Unit of the National Institute of Donation and Transplantation. The results are presented as mean and standard deviation (SD) for the continuous variables;and qualitative variables are described with percentages. Result(s): Patient recruitment began in February 2018 and we have recruited 110 patients. The mean age at the time of biopsy was 38.3+/-16.1 (min:16;max:78) years. Regarding sex distribution, the female sex slightly predominated (55.3%). Plasma creatinine was 2.1+/-1.45 mg/dL, proteinuria was 3.1+/-3.7 gr/dL and albuminaemia was 3.2+/-1.0 mg/dL. Microhaematuria was present in 61% of patients in the sediment study. Figure 1 shows the negative impact of the COVID 19 pandemic on the incidence of patients undergoing kidney biopsy. IgA nephropathy (13,8%)was the most frequent primary glomerular disease, followed by d focal and segmental glomerulosclerosis and membranous nephropathy. Consernig the glomerulopathies secondary to a systemic disease, the most frequent diagnosis was lupus nephritis (34,5%) followed by vasculitis, amyloidosis and diabetes. Conclusion(s): Having a prospective cohort of patients with glomerular disease, including reliable data and biological samples, will allow us to perform clinical and epidemiological analyses quickly and reliably in the future. The data and aliquots of biological material are available to any local nephrologist who proposes a hypothesis and has the approval of the corresponding ethics committee. The medium-term objective is to incorporate other national reference institutions in the care of patients with glomerular diseases. The data collected by the Glomerular Biobank will be a valuable input to the process of continuous improvement, and will serve as a basis for future nephrological research of excellence. No conflict of interestCopyright © 2023

Kidney Biopsies during the Covid-19 Outbreak: A Series of Cases

Introduction: Kidney disease due to COVID-19 has been described with several presentations, both in acute phase and in posterior timing of the infection, and kidney biopsy is important for an ideal management. But the process of adequately perform a biopsy during the pandemic entails risks, as being the exposed and infected by the SARS-CoV-2. Besides of the usual potential complications, such as post-biopsy hemorrhage, that may require admission in an already crowded medical structure. For these reasons, attainment of kidney biopsies was limited to those who without an adequate histopathological diagnosis, were at higher risk of inappropriate management, as well as a pathology secondary to the SARS-CoV-2 could be ignored. The aim of this study is to perform a description of the cases biopsied during the SARS-CoV-2 pandemic, being emphasized those whose indication emerged because of the viral infection. Method(s): Descriptive study of the clinical presentation in addition to histopathological findings of cases requiring kidney biopsy during the period of March 2020 - July 2021. Result(s): A total of 37 cases were collected, with a median age of 40 years (range: 60), 51% males and 73% with known history of hypertension. A 35% of the cases presented nephrotic syndrome;with average proteinuria of 4189.5mg/24h. The most frequent histopathological diagnosis was focal segmental glomerulosclerosis (FSGS), accounting for 40% of the cases. 4 patients required biopsy after COVID-19. One of them presented with Acute Kidney Injury (AKI) during the acute phase of the SARS-COV-2 infection with prolonged hemodialysis requirement;presenting histopathological diagnosis of global and segmental glomerulosclerosis. Another case of AKI during the acute phase of infection and subsequent proteinuria presented global and segmental glomerulosclerosis with collapsing characteristics;while 2 cases due to nephrotic syndrome post-infection, presented histological data of minimal change disease and FSGS with acute tubular injury. Conclusion(s): Regardless of the appearance of a new pathology that affects the kidneys, the incidence of entities such as FSGS persists with greater frequency. However, that does not diminish the importance of performing renal biopsies, since this is an essential tool for management in cases where there is overlap of specific glomerual diseases with COVID-19. No conflict of interestCopyright © 2023

GROSS HEMATURIA AFTER COVID-19 mRNA VACCINATION: A PROSPECTIVE COHORT STUDY

Introduction: The effective control of coronavirus disease 2019 (COVID-19) can be achieved by implementing a global vaccination strategy. After millions of mRNA vaccines targeting severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have been administered worldwide, several reports have shown the cases with gross hematuria (GH) following the mRNA vaccine against SARS-CoV2 in patients with glomerulonephritis, especially immunoglobulin A nephropathy (IgAN). A total of 22 articles including 36 cases of GH after COVID-19 vaccination as on July 31, 2022, were found in PubMed and Google Scholar databases. The most cases which had performed kidney biopsy were IgAN or IgA vasculitis. So, it suggested that GH after COVID-19 vaccination is rerated IgAN. Although there are many reported cases of IgAN after COVID-19 vaccination, the detailed clinical characteristics and outcome have not determined in these patients. Moreover, it remains unclear whether COVID-19 vaccination causes the new onset of nephritis or exacerbates pre-existing nephritis. To address this, herein, we conducted a prospective cohort study over a six-month period. Method(s): We analyzed 82 patients who presented with GH after COVID-19 vaccination and conducted a 6-month observational study. Patients, 18 years or older, who presented to the hospital with GH after COVID-19 vaccination were recruited. All the patients visited either Juntendo University Hospital or Juntendo University Urayasu Hospital between May 11, 2021, and July 31, 2022. Result(s): During the study period, a total of 82 individuals who presented with GH after COVID-19 vaccination were enrolled. The median age of the patients was 38 years;58 cases (70.7%) were females. All the patients received an mRNA COVID-19 vaccine. Most patients showed GH within three days after the second or third dose. Among the 82 patients, 22 had been already diagnosed with IgAN or IgA vasculitis (IgAV) before vaccination, and 45 of the 60 undiagnosed patients had a history of abnormal urinary findings. We performed kidney biopsies on 42 of the 60 undiagnosed patients, who were then diagnosed with IgAN (N=41) or IgAV (N=1). Pathological findings demonstrated that chronic inflammation of glomeruli, such as the expansion of mesangial matrix and glomerular sclerosis, is similarly observed in these newly diagnosed patients compared to patients with IgAN unrelated to vaccination. Finally, we evaluated the levels of biomarkers known to be elevated in IgAN at diagnosis during the course of the study and found that they did not increase. Notably, only few cases showed a slight increase in the level of serum creatinine, and no patients progressed to severe renal dysfunction. Conclusion(s): Present prospective study with 82 cases with GH after COVID-19 vaccination have identified their clinical characteristics and outcome. Furthermore, the acute manifestation of vaccine-induced GH may have highlighted the high prevalence of undiagnosed or preclinical IgAN in Japan. No conflict of interestCopyright © 2023

A Case Report on Primary Collapsing Glomerulopathy in a Filipino Post-partum Female and An Updated Review of Literature

Collapsing Glomerulopathy (CG) is a rare entity presenting as nephrotic syndrome and rapidly progressive renal deterioration. It has been first identified among African-American patients and subsequently dubbed HIV-associated nephropathy after a number of patients with HIV were found to have CG. It has re-emerged recently among patients with COVID-19. To our knowledge, this is the first case of primary collapsing glomerulopathy in the country to be published. The case is a 36-year-old Filipino female admitted due to bipedal edema which started 2 weeks post-partum. She has no comorbidities and social history was negative for illicit drug use. Initial work up showed hypoalbuminemia and diffuse hepatic disease on ultrasound. She was referred to a gastroenterologist where albumin infusion and paracentesis was done but with no improvement. She developed anasarca and was admitted. Paracentesis obtained minimal ascitic fluid. Serum ascites albumin gradient was low and baseline laboratories showed high creatinine, hypoalbuminemia, and albuminuria. 24-hour urine protein was 11 grams, ANA and anti-DsDNA were negative and c3 and c4 levels were normal. Hepatitis profile was negative for infection. Abdominal CT scan revealed multiple hypoenhancing lesions. Tumor markers CA-125, CA 19-9 and CA 15-3 were high. Breast ultrasound showed simple breast cyst. Gynecology consult was called where pap smear was negative for atypical cells. Surgery service recommended monitoring for the pancreatic and breast lesions. Kidney biopsy was delayed due to new onset bacterial pneumonia. COVID-19 RT-PCR test was negative. Patient was discharged improved with no edema. On follow up, the kidney biopsy result came out to be collapsing glomerulopathy. HIV test was then done and was negative. Bipedal edema and albuminuria recurred. She was started on tacrolimus. She has been on regular follow up and currently has no edema, no proteinuria and normal creatinine level. This is an interesting case as the primary glomerular disease has been masked by the earlier laboratory findings which led us to think of liver disease then a paraneoplastic nephrotic syndrome. Ultimately, the renal biopsy revealed the diagnosis. This serves as an index case for primary collapsing glomerulopathy in a Filipino patient on remission after being treated with tacrolimus. © 2023 University of the Philippines Manila. All rights reserved.

Covid-19 Infection in Peritoneal Dialysis Patients: Epidemiological and Clinical Profile, Risk Factors and Mortality

Introduction: Since the beginning of the coronavirus infection 2019 (COVID-19) pandemic, the population of dialysis patients has been recognized as a population at high risk of infection due to immune background and comorbidities. This study aims to describe the epidemiological characteristics, mortality and risk factors for COVID-19 infection in this population. Study design: Retrospective cohort study Methods: Patients on peritoneal dialysis in a university hospital center tested positive for coronavirus-19 by PCR method by nasopharyngeal swab from January 2020 to June 2022. Epidemiological and medical data collected from computerized medical records and from the Registry of French language peritoneal dialysis. Analytical approach: Logistic regression analyzes conducted to identify epidemiological and clinical characteristics associated with COVID-19 and risk factors associated with COVID-19 infection Results: 21 (31.8%) patients on peritoneal dialysis developed COVID-19. The male sex was slightly predominant with 11 men (52.4%). The average age of the patients was 67.48 years +/- 16.48, the average body mass index of the patients affected was 24.26, the average length of seniority in dialysis of the patients was 2.54 years +/- 1.3 years. The predominant initial nephropathy was diabetic nephropathy, glomerulosclerosis, IgA nephropathy and interstitial nephropathy with rates of 38.1%, 19%, 9.5% and 9.5% respectively. The risk factors for covid infection found were: an antecedent of ischemic cardiopathy, the diabetic nephropathy Conclusion(s): While it is true that Sars-cov 2 infection and its complications have increased the mortality rate in most dialysis centres, it should be noted that other factors have contributed to the increase in mortality such as socioeconomic circumstances related to financial financial difficulties, missed consultation appointments secondary to the apprehension of contracting the disease while traveling to the centers as well as the difficult due to confinement. No conflict of interestCopyright © 2023

Covid-19 Vaccination Induced Minimal Changed Disease

Introduction: Minimal change disease (MCD) accounts for approximately 15% of adults with idiopathic nephrotic syndrome (NS). We report the case of minimal change disease in a patient who presented with signs and symptoms of NS following Covid-19 immunisation vaccine. Method(s): Case: A 58-year-old male with negligible past medical history developed generalised swelling 2 days following receiving the Pfizer Covid-19 booster. On examination, he had a blood pressure of 130/80 and anasarca. Relevant laboratory results include a creatinine of 123, estimated glomerular filtration rate (eGFR) of 55, albumin of 9, urine protein: creatinine ratio of 713, and hyaline casts of moderate quantity. A kidney biopsy revealed glomerular sclerosis appropriate for age, and normal vessels and tubules. Immunofluorescence showed negative serology. A diagnosis of minimal change disease was made. The patient was treated with high dose prednisone at 1mg/kg/day and went into remission. The patient was followed up 2 months after admission, and investigations revealed a creatinine of 70, eGFR of >90, albumin of 34 and urine protein:creatine ratio of 58. Result(s): / Conclusion(s): Discussion and conclusion: This is the first case of Covid-19 vaccination induced NS reported in New Zealand. Theorised mechanism of injury includes T-cell mediated immune dysregulation, leading to glomerular disease (Sahin et al., 2020). Different glomerular diseases have been reported to occur for the first time following the Covid-19 vaccination (Klomjit et al., 2021). There has also been reports of reactivation of disease following Covid-19 immunisation (Hartley et al., 2022 and Leong et al., 2021). mRNA vaccination induced NS should be considered in all patients presenting with apparent idiopathic NS. This is especially important as we continue to learn more about the Covid-19 vaccination. No conflict of interestCopyright © 2023

Collapsing focal segmental glomerulosclerosis secondary to COVID-19: A systematic review and meta-analysis.

The renal system manifestations of coronavirus disease-2019 have been documented extensively; however, scientific literature remains scarce regarding collapsing glomerulopathy hence the need for this investigation. Methods: A comprehensive review was conducted covering a timeline from 1 January 2020 to 5 February 2022 without any restrictions. The data extraction was conducted independently, and articles were assessed for the risk of bias. Data analysis was conducted using Comprehensive Meta-Analysis version 3.3.070 and RevMan version 5.4 for pooled proportions and risk ratio (RR) between dialysis-dependent and independent treatment groups with a P-value less than 0.05 considered significant. Results: A total of 38 studies were included in this review, including 74 (65.9%) males. The mean age was 54.2 years old. The most common symptoms reported were related to the respiratory system (59.6%, 95% CI: 50.4-68.2%) and hematuria (34.2%, 95% CI: 26.1-43.4). Antibiotics (25.9%, 95% CI: 12.9-45.3%) was the commonest management used. Proteinuria was the most reported laboratory finding at 89.5% (95% CI: 82.4-93.9%), while the commonest microscopic finding was acute tubular injury (77.2%, 95% CI: 68.6-84.0%). An increased risk of the presence of symptoms (P=0.005) and microscopic findings (P=0.0003) related to collapsing glomerulopathy in dialysis-dependent group was noted with increased management (P=0.01) used in this group for coronavirus disease-2019 infection. Conclusion: The findings of this study portray the prognostic value of the variables (symptoms and microscopic findings, etc.) reported in the analysis. Hence this study serves as a foundation for future investigations that minimize the study's limitations to provide a more robust conclusion.

SARS-CoV-2 infection of kidney tissues in some severe and fatal cases of COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to diverse clinical manifestations and pathologies that involve multiple organs. Even though the disease severity is manifested mainly in the respiratory tract, which is the primary target of SARS-CoV-2 infection, acute kidney injury in the form of acute tubular necrosis has also been noted in some COVID-19 cases. It is not entirely clear whether renal cells can be infected by the virus that might be involved in acute kidney disorder. In a recent publication by Radovic and colleagues, that has been selected as the editor's choice paper published in the Journal of Medical Virology, the authors provided strong histopathological and immunofluorescence evidence of SARS-CoV-2 infection and tissue injury of renal parenchymal and tubular epithelial cells, which strongly suggest an active viral replication in the kidney of some severe and fatal COVID-19 cases, and to a lesser extent, a potential role for innate immune cells in viral infection and renal disease pathogenesis.

MALIGNANT HYPERTENSION AFTER COVD-19 VACCINE INJECTION

Case;40 y/o male. Clinical course;The patient was transferred to our university hospital because of DOE and severe headache. He had been well and had no history of hypertension or obesity. He had experienced the COVID-19 vaccine injection two week before this visit. After the injection he had been experienced high fever and general fatigue as well as 7 kg of weight loss. On examnation, it was found that he had severe hypertension (190/110 mmHg) and hypertensive optic fundi. On chest X-ray, cardiomegaly and bilateral lung infiltrations was evident and biochemical data indicated renal dysfunction (serum creatinine 2.35 mg/dl), high levels of plasma renin activity (39.1 ng/ml/hour normal;0.6-3.9) and aldosterone concentration (176 pg/ml normal;4.0-82.1), and inflammatory changes (CRP = 23 mg/dl). We also found that increased levels of LDH and decreased levels of hemoglobin which indicated hemolytic anemia and thrombotic microangiopathy. After the control of high blood pressure by intravenous administration of Calcium channel blockades, We performed renal biopsy, which had a finding of diffuse findings of onion skin lesion and global glomerular sclerosis compatible with the diagnosis of malignant hypertension. Any secondary etiologies including renal artery disease or collagen disease had not been identified. Seven days after the admission, we started hemodialysis for this patient because of the renal failure was not resolved. We also had startred ACE inhibitors. We stopped the diuretics and minimized the ultrafiltration. Twenty-five days after the admission the patients was withdrawn from dialysis with the urine volume around 2000 ml/day and the serum creatinine concentration 5.29 mg/dl. He was discharged without any aid of dialysis and with small number of anti-hypertensives. Four months after the discharge, his serum creatinine concentration was 3.36 mg/dl and his blood pressure was 139/85 mmHg with the ACE inhibitor and calcium channel blockades. Conclusions;The case suggested that the malignant hypertension might be triggered by COVID-19 vaccine injection, which is of clinical importance.

SARS-CoV-2 infection of kidney tissues from severe COVID-19 patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) manifests diverse clinical pathologies involving multiple organs. While the respiratory tract is the primary SARS-CoV-2 target, acute kidney injury is common in COVID-19 patients, displaying as acute tubular necrosis (ATN) resulting from focal epithelial necrosis and eosinophilia, glomerulosclerosis, and autolysis of renal tubular cells. However, whether any renal cells are infected by SARS-CoV-2 and the mechanism involved in the COVID-19 kidney pathology remain unclear. METHODS: Kidney tissues obtained at autopsy from four severe COVID-19 patients and one healthy subject were examined by hematoxylin and eosin staining. Indirect immunofluorescent antibody assay was performed to detect SARS-CoV-2 spike protein S1 and nonstructural protein 8 (NSP8) together with markers of different kidney cell types and immune cells to identify the infected cells. RESULTS: Renal parenchyma showed tissue injury comprised of ATN and glomerulosclerosis. Positive staining of S1 protein was observed in renal parenchymal and tubular epithelial cells. Evidence of viral infection was also observed in innate monocytes/macrophages and NK cells. Positive staining of NSP8, which is essential for viral RNA synthesis and replication, was confirmed in renal parenchymal cells, indicating the presence of active viral replication in the kidney. CONCLUSIONS: In fatal COVID-19 kidneys, there are SARS-CoV-2 infection, minimally infiltrated innate immune cells, and evidence of viral replication, which could contribute to tissue damage in the form of ATN and glomerulosclerosis.

Anti-Gbm Disease One and Half Years Experience in a Tertiary Care Centre

BACKGROUND: Anti-glomerular basement membrane (GBM) antibody GN is a rare glomerular disease (0.5-1 per million population) with poor outcome in terms of renal survival. It is caused by auto-antibodies against the non-collagenous domain of the a3 chain of type IV collagen and usually present as a rapidly progressive crescentic GN. Anti-GBM GN may present either as an isolated kidney disease or as a pulmonary-renal syndrome (Goodpasture's syndrome) in 40%-60% of patients. Linear staining of the GBMs for immunoglobulin ( Predominantly IgG & rarely IgA ) in renal biopsy with anti-GBM antibodies in serum is pathognomonic of Anti-GBM disease. Initiating immunosuppression with steroids and cyclophosphamide plus plasmapheresis are the cornerstone of treatment whereas no treatment is recommended if dialysis dependent at presentation 100% crescents or >50% global glomerulosclerosis in an adequate biopsy sample or not having pulmonary hemorrhage. AIM OF THE STUDY: To study demographic and clinical profile treatment administered and outcome (in terms of renal survival) in the patients with biopsy-proven anti-GBM disease. METHOD(S): Single-center prospective observational study (January 2021 to June 2022 ) and study population being the admitted patients in Nephrology Department of I.P.G.M.E.R and SSKM hospital Kolkata. RESULT(S): Total 7 patients were diagnosed as having Anti- GBM disease in this time period with median age of 42 yrs ( range from 11 yrs to 68 yrs), and Female : Male ratio was 5:2. Rapidly Progressive Renal Failure with Oliguria (71.4% ) was the most common presentation and 85.7% required Hemodialysis on presentation. 57.1% patients had 100% crescent in renal biopsy. 1 out of 7 patients had overlap with MPO and did not required RRT at presentation. 1 out of 7 patients had associated pulmonary hemorrhage. 28.5% patients received PLEX while others were treated supportively as per protocol. 28.5% patients previously had COVID 19 infection which was diagnosed retrospectively by detecting COVID 19 IgG antibody in serum. 71.4% patients end up in HD requiring renal failure while 1 patient succumbed to death. CONCLUSION(S): Most of the patients aged between 20 yrs to 60 yrs and were female (both 71.4%). Most of the patients (71.4%) received supportive treatment as per protocol. Only 1 patient (with MPO overlap) is dialysis free with discharge creatinine of 3.3 and receiving EUVAS protocol. Most of the patients who presented late with HD requiring renal failure end up in ESRD.

Histological Presentations of Post Covid Aki: A Spectrum of Presentations

BACKGROUND: Covid 19 is relatively a new disease with varied presentations which can affect multiple organs including kidney. AKI is quite commonly associated with covid-19 infection. However, a lot of research is still needed in understanding of the pathophysiology associated. AIM OF THE STUDY: To study the histological patterns of covid-associated AKI. METHOD(S): This is a retrospective longitudinal study. 109 patients developing AKI after covid -19 infection have been identified. AKI was defined as per KDIGO criteria. Evaluation of AKI was done with routine analysis, and causes other than covid infection were ruled out. Renal biopsy was done, and core specimens were sent for light microscopy and immunofluorescence. RESULT(S): Patients varied from 2 to 76 years. The duration between Covid infection and AKI ranged from 2 weeks to 6 months. Out of 109 patients, 27 (24.7%) showed acute tubular injury, 26 (23.8) showed ATIN, 11 (10%) showed IRGN, 8 (7%) showed crescentic GN, 4 (3.6%) showed chronic TIN,6 (5.5%) showed TMA, 3 (2.75%) showed Ig A nephropathy and Granulomatous TIN each. FSGS and cast nephropathy were seen in 4 (3.6%) patients each. Lupus nephritis, MCD, and Papillary necrosis were seen in one patient each. Rest of the patients, i.e., 10 (9.1%), showed features of background disease. CONCLUSION(S): AKI followed by covid 19 has a variety of pathologic mechanisms. Studying the patterns and their further follow-up will be beneficial since there is very limited data.